This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Subproject #2: Immune Correlates of BKV Persistence and Reactivation John A. Vanchiere BK virus (BKV) has emerged as an important cause of morbidity in kidney and stem cell transplant recipients, and this emergence has underscored the significant deficits in our knowledge of the natural history of this ubiquitous virus. Asymptomatic reactivation and shedding of BKV is common during periods of immune compromise, including pregnancy, but the host immune factors that normally maintain BKV latency are poorly understood. BKV reactivation during pregnancy presents a unique opportunity to explore the immune activation associated with BKV shedding and the host factors that influence transmission of BKV during early childhood without the confounding factors associated with organ transplantation and severe immune compromise. The central hypothesis of this proposal is that maternal immune factors contribute to the reactivation of BKV during pregnancy, ultimately influencing the transmission of BKV from mother to child. These studies will define the natural history of BKV infection in humans, including the identification of events in early infancy that facilitate BKV transmission, the immune pathways activated in response to maternal BKV reactivation and the infant immune response to BKV infection. An improved understanding of the natural history of BKV infection is crucial to the development of future studies of the pathogenesis and treatment of BKV-related disease.